This is a competing renewal application for the Claude D. Pepper Older Americans Independence Center at the University of Michigan (UM Pepper Center). The specific aims of the UM Pepper Center are: 1) To support research which has a focus on enhancing the independence of older adults by improved understanding of predictors and modulators influencing the development of aged phenotypes, including healthy aging and a range of disablement outcomes. 2) To help maintain and restore the independence of older people by supporting translational research linking basic with clinical research on aging and common health problems of older adults leading to disability. 3) To provide Resource Cores (RCs) to support and assist investigator initiated research projects which can lead to new insights into the basic mechanisms underlying conditions that contribute to aged phenotypes including comorbidity and loss of independence and which develop and test innovative methods to apply to such research projects. 4) Through its Research Career Development Core (RCDC), to strengthen the UM environment for training of future academic leaders who will conduct research on mechanisms contributing to aged phenotypes, and initiate translational research to enhance independence of older adults. 5) Through its Pilot and Exploratory Studies Core (PESC), to attract UM junior faculty (or selected senior faculty not previously involved in aging research) to study problems predisposing to aged phenotypes and to carry out translational research to reduce disablement outcomes. The UM Pepper Center, now in its 20"^ year of continuous NIA funding, has in place a well established leadership and administrative structure, an RCDC, a PESC, and four RCs: the Human Subjects and Assessment Core;the Biomechanics Core;the Methodology, Data Management and Analysis Core;and the Core Facility for Aged Rodents. There is outstanding institutional support, including a UM commitment of almost $2 million of direct costs over the proposed 5 years of this renewal. The RCDC features three central elements: 1) a competitive program to select promising UM junior faculty for salary support to conduct research relevant to the UM Pepper Center's research focus;2) a nationally recognized research training program for junior faculty engaged in such research, and 3) a Mentorship Program that enhances opportunities for junior faculty members to work closely with one or more UM senior investigators. The PESC, through rigorous external review, will fund 5 or more pilot projects per year. The RCs will support 23 externally funded projects, the Pepper Center pilot grants and RCDC junior faculty, and continue to develop and test new methods to be used in Pepper Center research.